When the Renaissance physician Andreas Vesalius wrote his magnum opus on human anatomy in 1543, he transformed the study of medicine and revolutionised the way scientists investigate the world.

A “mind-blowing” edition of his De Humani Corporis Fabrica Libri Septem, estimated to be worth up to £1m, is to be sold at auction for the first time since scholars discovered it was annotated by Vesalius himself.

The fragile, 800-page book was last sold in 2007 for about £8,500 to Dr Gerard Vogrincic, a retired Canadian pathologist and medical history buff who collects old annotated medical books.

He noticed the entire text, which earned Vesalius a reputation as the “father of modern human anatomy”, was heavily annotated in Latin from beginning to end, with unusual crossings-out of paragraphs, tiny amendments to drawings and corrections of punctuation and spelling errors. “It was quite remarkable,” he said.

“There were many pages that were filled with annotations and often what was being written in the margin was being crossed out and rewritten again. It was not what an annotator would typically do, which is underlining and making marginal notes to highlight important information. What this person was doing was rewriting the book.”

Unable to read Latin, Vogrincic decided to compare the handwriting of the annotator with other known examples of Vesalius’s handwriting. When more than 100 words appeared to be an identical match, he contacted the renowned Vesalius expert Prof Vivian Nutton, at the UCL Centre for the History of Medicine, who read and studied the annotations – and confirmed they were indeed made by Vesalius.

“As soon as you see the sheer number of all those corrections, it’s mind-blowing,” Nutton said, adding that some of the annotations were instructions to the printer while others were notes and indications “that only the author could have made”.

“There’s completely no doubt.”

He said reading the annotations offered a unique opportunity to “get absolutely into mind of Vesalius. You can see how he thinks, what’s interesting to him, why he’s trying to do something.”

Vogrincic had no idea when he bought the book that Vesalius had ever touched it, let alone annotated it, but he wanted it for his collection regardless. He said: “This book changed the way medicine was thought about. Before Vesalius wrote it, people just assumed that the ancient Greek physicians, Hippocrates and Galen, were the authorities – and shouldn’t be questioned.”

Galen, who was born in AD129, dominated the study of anatomy for a millennium – even though he based his anatomical reports mainly on the dissection of animals such as barbary apes. His inaccuracies persisted because most professors of anatomy, who read and taught Galen to university students, did not carry out dissections themselves. That was seen as manual labour, and so left to surgeons.

Vesalius, whose medical genius earned him a professorship at 23, had “a completely different mindset”, said Vogrincic. “He had to see for himself. And the more he looked and did his own dissections, he saw that Galen was wrong. And that’s when he started to question all of the authority that had come down over the ages and say: we have to find out for ourselves what the truth is.”

When Vesalius published his highly controversial discoveries in the Fabrica at the age of 28, he intertwined his text with detailed illustrations of the human anatomy, which were “unsurpassed at the time in beauty and accuracy and quality”, said Vogrincic.

Physicians continued to rely on his anatomy illustrations for more than 200 years. “It’s a remarkable piece of work, far in advance of anything else available at the time,” said Nutton. “He quickly produced a system of anatomy and put it forward in a totally different and unique way.”

Vesalius published a second edition of the Fabrica in 1555, and scholars have concluded that the copy being offered for auction at Christie’s in New York on Wednesday was annotated by the author in preparation for a third edition.

“These are notes partly that he made for the printer – but entirely for himself,” said Nutton, who spent two years studying the annotations, before other scholars were given access to the book via the University of Toronto’s Thomas Fisher Rare Book Library, where it was housed for over a decade.

This enabled Vogrincic to share his discovery with the world, while ensuring he could still afford to own it. “Book collectors dream about a find like this and it certainly was exciting. But to insure a book that valuable in the house – the cost is outrageous,” he said.

A third edition of the Fabrica was never published due to Vesalius’s untimely death at the age of 50 in a shipwreck. Scholars now regard this unique annotated copy as Vesalius’s final revisions to his famous text. “I’d be afraid to have it in my home now, afraid to look at it and afraid there would be a fire in the house. It’s too important, and too expensive,” said Vogrincic.

“It’s like owning the crown jewels.”